The primary goal of this study is to explore the role of fractionation and other potentially influential factors in the expression of radiation-induced damage to growing bone to predict appraoches which would improve therapeutic index in the treatment of pediatric malignancies. Using a rat model, a variety of experiments will be performed in order to: better define the tissue-sparing potential of hyperfractionated radiation schedules; clarify the mechanisms of damage of fractionated irradiation by observing the relationship between dose and fractionation schedule and a variety of histopathological endpoints; and study the influence of dose, fractionation, beam energy and concomitant drug therapy on the repair capacity of various tissue compartments (chondrocytes, microvasculature, osteocytes, matrix, et.). In these experiments, histomorphometric methods of analysis will be exploited to permit quantification of histological endpoints in a large number of specimens. Development and application of morphometric techniques to determine radiation dose-response relationships in this complex system may provide a useful tool for the analysis of radiation-induced normal tissue damage in general.